Window into Microbial Behavior

By Roberta Friedman, PhD

We know they are there, but most microbial denizens of deep oceans, sea floor vents, even our own intestines, remain a mystery. Because most microbes won’t grow in the lab, researchers have few clues to their communal activities.

With better gene sequencing and computational ability, researchers now sample genes from whole communities to assem- ble the “metagenome”—a picture of the genes driving metabolic processes important to growth and survival in a given environment.

In a new study, researchers found remarkable diversity in how microbes function in each of nine distinct biomes. Indeed the bacterial and viral genomes from each biome had distinguishing metabolic profiles. And viral genomes— which researchers expected would be similar across environments—were just as different as the bacteria.

It turns out that there’s a surprisingly extensive genetics arms race going on between bacteria and the viruses (called phages) that infect them, says Rob Edwards, PhD, assistant professor in the Computational Sciences Research Center at San Diego State University. Viruses are actively shuffling their host bacteria’s DNA. “We didn’t know (just) how much DNA the viruses move around,” Edwards says. In fact, it happens so often that, he believes, the viruses likely profit from moving pieces of DNA that are beneficial to the bacteria.

Edwards and his collaborators from San Diego State University, Argonne National Laboratory and around the world reached these conclusions by comparing nearly 15 million sequences from 45 microbial communities, including 42 viral genomes, as reported in Nature on April 3, 2008. It’s easy and relatively inexpensive to generate a DNA sequence these days, Edwards says, “What is not so easy is to figure out what it actually means.”

Thanks to the SEED database (www.theseed.org), developed in collaboration with researchers at Argonne Labs and the Fellowship for Interpretation of Genomes, which annotates or assigns known function to gene locations, scientists can upload gene sequence data and seek a pattern of metabolic activities that exist in their samples. They can thereby begin to compile the collective activities of a given community, be it a coral reef, a mine shaft, or a person’s bronchi.

This sort of work will definitely help researchers understand and harness the functions of bacteria, says Eric Delwart, PhD, a virologist at the Blood Systems Research Institute and the department of Laboratory Medicine at the University of California, San Francisco.

“Bacterial genomes are scrambled and slapped together by viruses. The core functions probably cannot be exchanged, but peripheral functions can be passed around,” he says, in a process unique to bacteria that likely speeds up their rate of evolution.

Such gene swapping may also yield therapeutic insight. A lot of diseases, such as atherosclerosis and stomach cancer, have “a very strong microbial component,” Edwards says. “We are working with the NIH to get at the bioinformatics of this.”